Use of mirna-2911 molecule as nucleic acid stabilizer

Abstract

The present invention relates to a use of a miRNA-2911 molecule as a nucleic acid stabilizer. Specifically, the structure of the miRNA-2911 molecule for improving the stability of a target nucleic acid is shown in the following formula: GGX1X2GGGGG-(L)n-X3X4GGX5X6X7GGGX8 (SEQ ID NO: 1), wherein X1, X2, X3, X4, X5, X6, X7, and X8 are independently selected from A, C, T, and U; n is 0 or 1; and L represents a linker group having a length of no more than 10 nucleotides.

1 . A miRNA-2911 and the nucleic acid molecule derived therefrom for improving the stability of a nucleic acid of interest, wherein the nucleotide sequence of the miRNA-2911 and the nucleic acid molecule derived therefrom comprises the following nucleic acid sequence: 
       
         
           
                 
                 
               
                     
                   (SEQ ID NO: 1) 
                 
                     
                   GGX 1 X 2 GGGGG-(L) n -X 3 X 4 GGX 5 X 6 X 7 GGGX 8   
                 
             
                
                
               
            
           
         
         wherein: 
         X 1 , X 2 , X 3 , X 4 , X 5 , X 6 , X 7  and X 8  are independently selected from A, C, T and U; 
         n is zero or 1; 
         L represents a linker group of no more than 10 nucleotides in length. 
       
     
     
         2 . The miRNA-2911 and the nucleic acid molecule derived therefrom according to  claim 1 , wherein represents GGGGG. 
     
     
         3 . The miRNA-2911 and the nucleic acid molecule derived therefrom according to  claim 1 , wherein the miRNA-2911 and the nucleic acid molecule derived therefrom comprise the following nucleic acid sequence: 
       
         
           
                 
                 
               
                     
                   (SEQ ID NO: 3) 
                 
                     
                   GGX 1 X 2 GGGGGX 3 X 4 GGX 5 X 6 X 7 GGGX 8   
                 
             
                
                
               
            
           
         
         wherein: 
         X 1 , X 2 , X 3 , X 4 , X 5 , X 6 , X 7  and X 8  are independently selected from A, C, T and U. 
       
     
     
         4 . The miRNA-2911 and the nucleic acid molecule derived therefrom according to  claim 1 , wherein:
 X 1 , X 2 , X 4  and X 6  are identical, optionally are A, C or U; and/or   X 3 , X 5  and X 8  are identical, optionally are A, C or U.   
     
     
         5 . The miRNA-2911 and the nucleic acid molecule derived therefrom according to  claim 1 , wherein the sequence of the miRNA-2911 and the nucleic acid molecule derived therefrom is as shown in any one of SEQ ID NO: 2, and SEQ ID NO: 4-10. 
     
     
         6 . A protected nucleic acid of interest, wherein:
 the miRNA-2911 and the nucleic acid molecule derived therefrom according to  claim 1  are conjugated to the 5′ and/or 3′ end of the nucleic acid of interest, or   the miRNA-2911 and the nucleic acid molecule derived therefrom according to  claim 1  are inserted into the nucleic acid of interest;   and the stability of the protected nucleic acid of interest is improved.   
     
     
         7 . The protected nucleic acid of interest according to  claim 6 , wherein:
 the nucleic acid of interest is ≥8 nt in length; and   the nucleic acid of interest is a nucleic acid for gene knockdown, a nucleic acid for gene knockout, a nucleic acid for gene activation, a nucleic acid for gene modification, a nucleic acid for gene editing, a nucleic acid for gene regulation, a nucleic acid for protein regulation, a nucleic acid for protein expression, a nucleic acid for bioassay, or a nucleic acid drug.   
     
     
         8 . A pharmaceutical composition, wherein the pharmaceutical composition comprises:
 (1) a therapeutically effective amount of the protected nucleic acid of interest according to  claim 6 , and   (2) a pharmaceutically acceptable carrier.   
     
     
         9 . A method for improving the stability of a nucleic acid of interest, wherein:
 the miRNA-2911 and the nucleic acid molecule derived therefrom according to  claim 1  are conjugated to the 5′ end and/or 3′ end of the nucleic acid of interest, or inserted into the nucleic acid of interest.   
     
     
         10 . A The method according to  claim 9 , wherein:
 the nucleic acid of interest is ≥8 nt in length; and   the nucleic acid of interest is a nucleic acid for gene knockdown, a nucleic acid for gene knockout, a nucleic acid for gene activation, a nucleic acid for gene modification, a nucleic acid for gene editing, a nucleic acid for gene regulation, a nucleic acid for protein regulation, a nucleic acid for protein expression, a nucleic acid for bioassay or a nucleic acid drug.   
     
     
         11 . The method according to  claim 9 , wherein the nucleic acid of interest is:
 (1) an oligonucleotide, including but not limited to an antisense oligonucleotide ASO or an apatmer; or   (2) a single-stranded DNA, a double-stranded DNA, a single-stranded RNA, a double-stranded RNA, an mRNA or an ncRNA; the ncRNA includes but not limited to miRNA, siRNA, saRNA, piRNA, incRNA, circRNA, fragments thereof, or other regulatory RNA.   
     
     
         12 . The protected nucleic acid of interest according to  claim 6 , wherein the nucleic acid of interest is:
 (1) an oligonucleotide, including but not limited to an antisense oligonucleotide ASO or an apatmer; or   (2) a single-stranded DNA, a double-stranded DNA, a single-stranded RNA, a double-stranded RNA, an mRNA or an ncRNA; the ncRNA includes but not limited to miRNA, siRNA, saRNA, piRNA, lncRNA, circRNA, fragments thereof, or other regulatory RNA.